Day 2 | Five Critical Points You MUST Check When Selecting an Oligonucleotide CDMO ⁉️

🔬🔬 Day 2 | Five Critical Points You MUST Check When Selecting an Oligonucleotide CDMO ⁉️
Choosing a CDMO for oligonucleotide development based only on:
✔ Low cost
✔ Fast turnaround
✔ Acceptable purity and yield
✔ “Passing” analytical reports
‼️can lead to serious problems during in vitro, in vivo, or scale-up stages. Many failures arise from misinterpreting quality data. Below are five common technical pitfalls to watch for:‼️

① Purity value ≠ True product quality
A statement like “95% purity” is meaningless unless impurity species (N-1, N-type, FP-related) are structurally identified. Without this, you cannot evaluate:
✔ Actual product quality
✔ Stability and behavior during scale-up
Most failures result not from low purity, but from not understanding what the purity contains.

② Analytical methods must be transparent
Different methods (HPLC, UPLC, LC-MS, IEX) can produce very different “94% purity” results. Analytical reports should clearly specify:
✔ Method used
✔ Peak identification criteria
✔ RRT / retention time consistency
✔ Method robustness
Purity should also be assessed using mass-based approaches (TOF or MALDI), not only area-based chromatogram values.
‼️ Unclear impurity profiles can directly affect biological activity, toxicity, and in vivo study outcomes. ‼️

③ Scale-up performance must be proven
mg → g → kg scale-up data is essential. Confirm:
1. Impurity trends across scales
2. Purification load and efficiency changes
3. Verified purity/yield for AOC or POC conjugates
4. Continuous data flow from raw materials to IND
5. Batch and supply chain management
Many projects succeed at small scale but fail during scale-up due to increasing impurities, purification limitations, or yield loss.

④ GMP level and facility conditions are not uniform
GMP compliance differs across FDA / EMA / PMDA / NMPA / ISO-style systems. Confirm:
✔ Applicable regulatory standards
✔ Audit and inspection history
✔ Batch record availability
✔ Corrective action status
Cross-contamination must also be evaluated:
1. Is each step (synthesis → purification → analysis → UF → lyophilization) performed on oligo-dedicated equipment?
2. Is formulation/filling handled in dedicated aseptic facilities?

⑤ Technical communication quality matters
When issues arise, the CDMO should provide not just data, but:
✔ Root cause analysis
✔ Risk mapping
✔ Consistent data traceability
✔ Corrective and preventive plans
Success depends not only on technical capability, but also on the ability to clearly explain data and decision logic.

🎯 Summary
Oligonucleotide quality cannot be judged from a single purity value. What truly determines project success is:
✔ Reproducibility
✔ Scalability
✔ Structural knowledge of impurities
✔ Problem-solving and explanation capability
If you need support in evaluating or comparing CDMOs, feel free to reach out anytime.